AstraZeneca and Daiichi Sankyo’s datopotamab
deruxtecan reduced the risk of disease progression or death
by 37%, providing a 2-month median PFS benefit, and was well
tolerated in post-endocrine therapy setting
Positive results from the pivotal TROPION-Breast01 Phase III
trial showed that datopotamab deruxtecan (Dato-DXd) demonstrated a
statistically significant and clinically meaningful improvement in
progression-free survival (PFS) compared to investigator’s choice
of chemotherapy in patients with inoperable or metastatic hormone
receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC
2+/ISH-) breast cancer previously treated with endocrine-based
therapy and at least one systemic therapy.
These data will be shared today in the first of two
late-breaking presentations for datopotamab deruxtecan in a
Presidential Symposium at the European Society for Medical Oncology
(ESMO) 2023 Congress in Madrid, Spain (LBA11).
Datopotamab deruxtecan is a specifically engineered
TROP2-directed DXd antibody drug conjugate (ADC) being jointly
developed by AstraZeneca and Daiichi Sankyo.
In the dual primary endpoint analysis, datopotamab deruxtecan
reduced the risk of disease progression or death by 37% compared to
investigator’s choice of chemotherapy (hazard ratio [HR] 0.63; 95%
confidence interval [CI] 0.52-0.76; p<0.001) as assessed by
blinded independent central review (BICR). Median PFS was 6.9
months in patients treated with datopotamab deruxtecan versus 4.9
with chemotherapy. A consistent PFS benefit was observed across
subgroups. Results also showed a confirmed objective response rate
(ORR) of 36.4% in patients treated with datopotamab deruxtecan
compared to an ORR of 22.9% with chemotherapy.
For the dual primary endpoint of overall survival (OS), interim
results numerically favored datopotamab deruxtecan over
chemotherapy (HR 0.84; 95% CI 0.62-1.14), however, results did not
reach statistical significance at the time of this data cut-off.
The trial is ongoing to assess OS.
Aditya Bardia, MD, MPH, Director of Breast Cancer Research, Mass
General Cancer Center, Associate Professor of Medicine at Harvard
Medical School and investigator in the trial, said: “Despite the
initial benefit of endocrine therapy, most patients with
HR-positive, HER2-low or negative metastatic breast cancer will
eventually experience disease progression and require additional
treatment with chemotherapy. In the TROPION-Breast01 trial,
datopotamab deruxtecan reduced patients’ risk of disease
progression or death by more than a third and overall had fewer
treatment-related serious adverse events than standard
chemotherapy, illustrating its potential to become a new standard
of care in a treatment setting where there is a clinical unmet
need.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “With these TROPION-Breast01 results,
datopotamab deruxtecan has the potential to meaningfully improve
treatment expectations for patients with HR-positive, HER2-low or
negative metastatic breast cancer by offering them an effective and
better tolerated treatment option after endocrine therapy and only
one line of chemotherapy. We look forward to continuing discussions
with regulatory authorities with the goal of bringing this
TROP2-directed antibody drug conjugate to eligible patients as soon
as possible.”
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said:
“These statistically significant and clinically meaningful results
from the TROPION-Breast01 trial support datopotamab deruxtecan as a
new potential standard of care for patients with advanced
HR-positive, HER2-low or negative breast cancer in the
post-endocrine therapy setting. The results further validate the
portability of Daiichi Sankyo's DXd antibody drug conjugate
technology to additional targets such as TROP2, and we look forward
to potentially bringing our second antibody drug conjugate to
patients with breast cancer.”
Datopotamab deruxtecan demonstrated a favorable safety profile
over chemotherapy with no new safety concerns identified. Grade 3
or higher treatment-related adverse events (TRAEs) occurred in 21%
and 45% of patients in the datopotamab deruxtecan and chemotherapy
arms, respectively. The most common Grade 3 or higher TRAEs were
neutropenia (1%, 31%), stomatitis (6%, 3%), fatigue (2%, 2%) and
anemia (1%, 2%). In the datopotamab deruxtecan arm, the all grade
interstitial lung disease (ILD) rate was low (3%) and the majority
of events were low grade. There was one Grade 5 ILD event
adjudicated as drug-related by an independent committee. The
primary cause of death in this case was attributed to disease
progression by the treating investigator.
Summary of TROPION-Breast01 Efficacy Results
Datopotamab deruxtecan (n=365)
Investigator’s choice chemotherapy
(n=367)
PFS, as assessed by BICR
Median PFS (95% CI)
6.9 months (5.7-7.4)
4.9 months (4.2-5.5)
HR (95% CI)
0.63 (0.52-0.76)
p-value
p<0.0001
PFS, as assessed by
investigator
Median PFS
6.9 months
4.5 months
HR (95% CI)
0.64 (0.53-0.76)
OS
HR (95% CI) i
0.84 (0.62-1.14)
Confirmed ORR ii, iii
36.4%
22.9%
CR rate
0.5%
0%
PR rate
35.9%
22.9%
CI, confidence interval; CR, complete response; HR, hazard
ratio; ORR, objective response rate; OS, overall survival; PFS,
progression-free survival; PR, partial response i With median
follow-up of 9.7 months, OS data were not mature ii As assessed by
BICR iii ORR is (complete response + partial response)
After endocrine therapy, the most common prior treatments for
patients in the datopotamab deruxtecan and chemotherapy arms,
respectively, included one (63%, 61%) to two (37%, 38%) lines of
chemotherapy and CDK4/6 inhibitor inhibitors (82%, 78%). At the
July 17, 2023 data cut-off, 93 patients remained on treatment with
datopotamab deruxtecan and 39 remained on chemotherapy.
AstraZeneca and Daiichi Sankyo have two Phase III trials
evaluating datopotamab deruxtecan in triple-negative breast cancer
(TNBC). TROPION-Breast02 is comparing datopotamab deruxtecan to
chemotherapy in patients with previously untreated locally
recurrent inoperable or metastatic TNBC who are not candidates for
anti-PD1/PD-L1 therapy. TROPION-Breast03 is evaluating datopotamab
deruxtecan with and without durvalumab versus investigator’s choice
of therapy in patients with Stage I-III TNBC with residual disease
after neoadjuvant therapy.
HR-positive breast cancer Breast cancer is the most
common cancer in the world and a leading cause of cancer-related
death.1 More than two million breast cancer cases were diagnosed in
2020 with nearly 685,000 deaths globally.1
Breast cancer is considered HR-positive, HER2-low or negative
when tumors test positive for estrogen and/or progesterone hormone
receptors and negative or low for HER2 (measured as HER2 score of
IHC 0, IHC 1+ or IHC 2+/ISH-).2,3 HR-positive, HER2-low or negative
breast cancer is the most common subtype, accounting for more than
65% of diagnosed cases.2
Standard initial treatment for these patients is endocrine
therapy but most patients with advanced disease will develop
resistance, underscoring the need for additional options.4,5
Approximately 30% of patients diagnosed with HR-positive, HER2-low
or negative metastatic breast cancer are expected to live five
years after their diagnosis.2
TROP2 is a protein broadly expressed in several solid tumors,
including HR-positive, HER2-low or negative breast cancer.6 TROP2
expression is associated with increased tumor progression and poor
survival in patients with breast cancer.6,7
TROPION-Breast01 TROPION-Breast01 is a global,
randomized, multicenter, open-label Phase III trial evaluating the
safety and efficacy of datopotamab deruxtecan (6.0 mg/kg) versus
investigator’s choice of single-agent chemotherapy (eribulin,
capecitabine, vinorelbine or gemcitabine) in patients with
inoperable or metastatic HR-positive, HER2-low or negative (IHC 0,
IHC 1+ or IHC 2+/ISH-) breast cancer who have previously progressed
on or are not suitable for endocrine therapy per investigator
assessment and have received at least one systemic therapy.
The dual primary endpoints of TROPION-Breast01 are PFS as
assessed by BICR and OS. Key secondary endpoints include ORR,
duration of response, investigator-assessed PFS, disease control
rate and time to first subsequent therapy.
TROPION-Breast01 enrolled more than 700 patients at sites in
Asia, Europe, North America, South America and Africa. For more
information visit ClinicalTrials.gov.
Datopotamab deruxtecan (Dato-DXd) Datopotamab deruxtecan
(Dato-DXd) is an investigational TROP2-directed ADC. Designed using
Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab
deruxtecan is one of six lead ADCs in the oncology pipeline of
Daiichi Sankyo, and one of the most advanced programs in
AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is
comprised of a humanized anti-TROP2 IgG1 monoclonal antibody,
developed in collaboration with Sapporo Medical University,
attached to a number of topoisomerase I inhibitor payloads (an
exatecan derivative, DXd) via tetrapeptide-based cleavable
linkers.
A comprehensive development program called TROPION is underway
globally with more than 12 trials evaluating the efficacy and
safety of datopotamab deruxtecan across multiple tumors, including
non-small cell lung cancer, TNBC and hormone receptor-positive,
HER2-low or negative breast cancer. Beyond the TROPION program,
datopotamab deruxtecan is also being evaluated in novel
combinations in several ongoing trials. AstraZeneca is also
researching a potential diagnostic test to help identify patients
most likely to benefit from treatment with datopotamab
deruxtecan.
Daiichi Sankyo collaboration AstraZeneca and Daiichi
Sankyo entered into a global collaboration to jointly develop and
commercialize fam-trastuzumab deruxtecan-nxki in March 2019 and
datopotamab deruxtecan in July 2020, except in Japan where Daiichi
Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is
responsible for the manufacturing and supply of fam-trastuzumab
deruxtecan-nxki and datopotamab deruxtecan.
AstraZeneca in breast cancer Driven by a growing
understanding of breast cancer biology, AstraZeneca is starting to
challenge, and redefine, the current clinical paradigm for how
breast cancer is classified and treated to deliver even more
effective treatments to patients in need – with the bold ambition
to one day eliminate breast cancer as a cause of death.
AstraZeneca has a comprehensive portfolio of approved and
promising compounds in development that leverage different
mechanisms of action to address the biologically diverse breast
cancer tumor environment.
With fam-trastuzumab deruxtecan-nxki, a HER2-directed ADC,
AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in
previously treated HER2-positive and HER2-low metastatic breast
cancer and are exploring its potential in earlier lines of
treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve
outcomes with foundational medicines fulvestrant and goserelin and
aims to reshape the HR-positive space with next-generation SERD and
potential new medicine camizestrant as well as a potential
first-in-class AKT kinase inhibitor, capivasertib. AstraZeneca is
also collaborating with Daiichi Sankyo to explore the potential of
TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP inhibitor olaparib is a targeted treatment option that has
been studied in early and metastatic breast cancer patients with an
inherited BRCA mutation. AstraZeneca with Merck & Co., Inc.
(known as MSD outside the US and Canada) continues to research
olaparib in these settings and to explore its potential in earlier
disease.
To bring much-needed treatment options to patients with TNBC, an
aggressive form of breast cancer, AstraZeneca is evaluating the
potential of datopotamab deruxtecan alone and in combination with
immunotherapy durvalumab, capivasertib in combination with
chemotherapy, and durvalumab in combination with other oncology
medicines, including olaparib and fam-trastuzumab
deruxtecan-nxki.
AstraZeneca in oncology AstraZeneca is leading a
revolution in oncology with the ambition to provide cures for
cancer in every form, following the science to understand cancer
and all its complexities to discover, develop and deliver
life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers.
It is through persistent innovation that AstraZeneca has built one
of the most diverse portfolios and pipelines in the industry, with
the potential to catalyze changes in the practice of medicine and
transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day,
eliminate cancer as a cause of death.
AstraZeneca AstraZeneca is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialization of prescription medicines in
Oncology, Rare Diseases, and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca-us.com and follow the
Company on social media @AstraZeneca.
References
- Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN
Estimates of Incidence and Mortality Worldwide for 36 Cancers in
185 Countries. CA Cancer J Clin. 2021; 10.3322/caac.21660.
- National Cancer Institute. Surveillance, Epidemiology and End
Results Program. Available at:
https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
Accessed October 2023.
- Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2)
in Cancers: Overexpression and Therapeutic Implications. Mol Biol
Int. 2014;852748.
- Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors
Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone
receptor-positive, HER2-negative metastatic breast cancer. J
Cancer. 2020; 10.7150/jca.48944.
- Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade
in Advanced Hormone Receptor–positive, HER2-negative Breast Cancer
and Emerging Therapeutic Opportunities. Clin Cancer Res. 2022;
28(5):821-30.
- Goldenberg D, et al. The emergence of trophoblast cell-surface
antigen 2 (TROP-2) as a novel cancer target. Oncotarget.
2018;9(48): 28989-29006.
- Vidula N, et al. Trophoblast Cell Surface Antigen 2 gene
(TACSTD2) expression in primary breast cancer. Breast Cancer Res
Treat. 2022 Aug;194(3):569-575.
US-81578 Last Updated 10/23
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231023654115/en/
Brendan McEvoy +1 302 885 2677 Jillian Gonzales +1 302 885
2677
US Media Mailbox: usmediateam@astrazeneca.com
AstraZeneca (NASDAQ:AZN)
Historical Stock Chart
Von Jun 2024 bis Jul 2024
AstraZeneca (NASDAQ:AZN)
Historical Stock Chart
Von Jul 2023 bis Jul 2024